Phenotyping Asthma for Bronchial Thermoplasty: Airway Smooth Muscle Structure and Function

支气管热成形术的哮喘表型分析：气道平滑肌结构和功能

基本信息

批准号：
10205149
负责人：
Melissa J Suter
金额：
$ 72.36万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10205149
关键词：
3-Dimensional Adrenal Cortex Hormones Affect Agonist Assessment tool Asthma Award Birefringence Bronchoconstriction Bronchodilator Agents Calibration Catheters Clinical Clinical Research Complex Computer software Custom Detection Disease Economic Burden Epithelial Etiology Evaluation Exhibits Extrinsic asthma Fiber Fibrosis Functional disorder Goals Human Hyperplasia Hypertrophy Imaging Device Imaging technology Individual Inflammation Knowledge Link Measures Metaplasia Monitor Morbidity - disease rate Mucous Membrane Mucous body substance Multi-Institutional Clinical Trial Multicenter Studies Muscle function Operative Surgical Procedures Optical Coherence Tomography Patients Phenotype Physiological Play Population Prevalence Research Research Proposals Resected Role Severity of illness Signal Transduction Structure Structure of parenchyma of lung Structure-Activity Relationship Symptoms System Technology Testing Therapeutic Thick Time Tissues Translating United States Visualization airway hyperresponsiveness airway inflammation airway obstruction airway remodeling asthmatic asthmatic patient base clinical predictors imaging platform imaging system improved in vivo individualized medicine muscular structure novel optical imaging preclinical study predicting response prospective public health relevance respiratory smooth muscle response sheep model socioeconomics targeted treatment three dimensional structure validation studies

项目摘要

Project Summary Asthma currently affects over 300 million individuals worldwide and the prevalence is continually increasing. Approximately 10% of asthmatics have uncontrolled or poorly controlled symptoms and it is this population that urgently need improved targeted therapies and management strategies in order to reduce the high morbidity and socio-economic burden, estimated to be 14.7 billion dollars annually in the United States alone. The exact mechanisms behind the pathophysiology of asthma remain uncertain. Airway smooth muscle (ASM) is known to play a critical and multifaceted role, yet our knowledge on the role of ASM in asthma is limited due to an inability to directly visualize and study the 3D structure of ASM, and the relationship to functional bronchoconstriction in patients. The real-time evaluation of ASM is critical in furthering our understanding of the pathophysiology of asthma, for classifying asthma phenotypes, for tailoring treatment, and for assessing and monitoring the response to therapy. In this award we will develop a custom optical imaging platform based on polarization-sensitive optical coherence tomography (PS-OCT) that will enable the accurate quantification of ASM hyperplasia and hypertrophy, epithelial disruption and hypertrophy, subepithelial fibrosis, mucosal thickness increases, mucus metaplasia, in vivo. We will develop and validate novel dual-layer calibrating catheters that will enable accurate assessment of tissue fiber orientation and birefringence signal intensity. We will additionally develop and validate automated calibration and processing software that will provide real-time visualization of ASM in vivo. These technological advancements will enable us to begin to answer important questions linking remodeling changes in airway wall structure with physiologic function. We will conduct a preclinical study in a sheep model of allergic asthma to test our hypothesis that remodeling plays both a protective and provocative role in bronchoconstriction, and that the presence of inflammation greatly increases bronchoconstriction. We will further translate this technology into the clinical setting in a multicenter clinical trial aimed at using our PS-OCT imaging system to phenotype asthma and to predict the response to bronchial thermoplasty. The unprecedented ability to study both the 3D structure of airway smooth muscle (ASM) and it’s function in vivo is likely to transform the study of asthma in patients in phenotyping populations, for therapy guidance, and in research endeavors aimed at studying the true role of ASM in asthma.

项目概要目前，全世界有超过 3 亿人患有哮喘，而且患病率还在不断增加。大约 10% 的哮喘患者有不受控制或控制不佳的症状，而正是这一人群迫切需要改进靶向治疗和管理策略，以降低高发病率据估计，仅美国每年就造成 147 亿美元的社会经济负担。哮喘病理生理学背后的机制仍不清楚。发挥关键和多方面的作用，但我们对 ASM 在哮喘中的作用的了解有限，因为无法直接可视化和研究 ASM 的 3D 结构以及与功能的关系 ASM 的实时评估对于加深我们对 ASM 的理解至关重要。哮喘的病理生理学，用于对哮喘表型进行分类、定制治疗和评估并监测对治疗的反应。在这个奖项中，我们将开发一个基于定制光学成像平台。偏振敏感光学相干断层扫描（PS-OCT），这将能够准确量化 ASM 增生和肥大、上皮破坏和肥大、上皮下纤维化、粘膜厚度增加，粘液化生，体内我们将开发和验证新型双层校准。能够准确评估组织纤维方向和双折射信号强度的导管。将另外开发和验证自动校准和处理软件，该软件将提供实时这些技术进步将使我们能够开始回答重要的 ASM 体内可视化问题。将气道壁结构重塑变化与生理功能联系起来的问题。在过敏性哮喘绵羊模型中进行的临床前研究，以检验我们的假设，即重塑既起到了作用在支气管收缩中具有保护和激发作用，并且炎症的存在大大增加我们将在多中心临床试验中进一步将这项技术转化为临床环境。旨在使用我们的 PS-OCT 成像系统对哮喘进行表型分析并预测对支气管哮喘的反应前所未有的研究气道平滑肌 (ASM) 3D 结构及其结构的能力。体内功能可能会改变表型人群中哮喘患者的研究，以用于治疗指导，以及旨在研究 ASM 在哮喘中真正作用的研究工作。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Polarization mode dispersion correction in endoscopic polarization-sensitive optical coherence tomography with incoherent polarization input states.

具有非相干偏振输入状态的内窥镜偏振敏感光学相干断层扫描中的偏振模式色散校正。

DOI：
10.1364/boe.457790
发表时间：
2022
期刊：
Biomedical optics express
影响因子：
3.4
作者：
Adams,DavidC;Majid,Adnan;Suter,MelissaJ
通讯作者：
Suter,MelissaJ

Automated segmentation and quantification of airway mucus with endobronchial optical coherence tomography.

DOI：
10.1364/boe.8.004729
发表时间：
2017-10
期刊：
Biomedical optics express
影响因子：
3.4
作者：
D. C. Adams;H. Pahlevaninezhad;M. Szabari;Josalyn L. Cho;D. Hamilos;M. Kesimer;R. Boucher;A. Luster;B. Medoff;M. Suter
通讯作者：
D. C. Adams;H. Pahlevaninezhad;M. Szabari;Josalyn L. Cho;D. Hamilos;M. Kesimer;R. Boucher;A. Luster;B. Medoff;M. Suter

Human milk H2O2 content: does it benefit preterm infants?